Inhibitors of bacterial tyrosyl tRNA synthetase: Synthesis of four stereoisomeric analogues of the natural product SB-219383

被引:32
作者
Berge, JM [1 ]
Copley, RCB [1 ]
Eggleston, DS [1 ]
Hamprecht, DW [1 ]
Jarvest, RL [1 ]
Mensah, LM [1 ]
O'Hanlon, PJ [1 ]
Pope, AJ [1 ]
机构
[1] SmithKline Beecham Pharmaceut, Harlow CM19 5AW, Essex, England
关键词
D O I
10.1016/S0960-894X(00)00348-6
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Synthetic analogues of the microbial metabolite SB-219383 have been synthesised with defined stereochemistry. Densely functionalised hydroxylamine containing amino acids were prepared by the addition of a glycine anion equivalent to sugar-derived cyclic nitrones. One of four stereoisomeric dipeptides incorporating these novel amino acids was found to be a potent and selective inhibitor of bacterial tyrosyl tRNA synthetase, suggesting analogous stereochemistry of the natural product. (C) 2000 Elsevier Science Ltd. All rights reserved.
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页码:1811 / 1814
页数:4
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